CN106496155B - A kind of aminothiazole quinoline chiral ligand and its preparation method and application - Google Patents
A kind of aminothiazole quinoline chiral ligand and its preparation method and application Download PDFInfo
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- CN106496155B CN106496155B CN201610932167.0A CN201610932167A CN106496155B CN 106496155 B CN106496155 B CN 106496155B CN 201610932167 A CN201610932167 A CN 201610932167A CN 106496155 B CN106496155 B CN 106496155B
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- chiral
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- aminothiazole
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- chiral ligand
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- 239000003446 ligand Substances 0.000 title claims abstract description 47
- FJFLPKJHOKJAAS-UHFFFAOYSA-N quinoline;1,3-thiazol-2-amine Chemical compound NC1=NC=CS1.N1=CC=CC2=CC=CC=C21 FJFLPKJHOKJAAS-UHFFFAOYSA-N 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 28
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 12
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 150000001414 amino alcohols Chemical class 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 5
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- 230000009435 amidation Effects 0.000 claims description 4
- 238000007112 amidation reaction Methods 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims description 2
- 238000006297 dehydration reaction Methods 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 230000010933 acylation Effects 0.000 claims 2
- 238000005917 acylation reaction Methods 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 239000003513 alkali Substances 0.000 claims 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 abstract description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 abstract description 2
- 239000004305 biphenyl Substances 0.000 abstract description 2
- 235000010290 biphenyl Nutrition 0.000 abstract description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
- QMXOFBXZEKTJIK-UHFFFAOYSA-N Glycinol Natural products C1=C(O)C=C2OCC3(O)C4=CC=C(O)C=C4OC3C2=C1 QMXOFBXZEKTJIK-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 238000001819 mass spectrum Methods 0.000 description 5
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- -1 benzene methylene malonic acid ester Chemical class 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- VPSSPAXIFBTOHY-LURJTMIESA-N (2s)-2-amino-4-methylpentan-1-ol Chemical group CC(C)C[C@H](N)CO VPSSPAXIFBTOHY-LURJTMIESA-N 0.000 description 1
- WBVPCMFFJMCPDD-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazole thiophene Chemical compound S1C=CC=C1.O1C=NCC1 WBVPCMFFJMCPDD-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical group NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical group OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 1
- ZIPLHLLDHUOMHV-UHFFFAOYSA-N O1C=NC=C1.P Chemical compound O1C=NC=C1.P ZIPLHLLDHUOMHV-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 229950003476 aminothiazole Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Chemical class 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical group [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/10—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
- B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
- B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
- B01J31/1815—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B53/00—Asymmetric syntheses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/006—Palladium compounds
- C07F15/0066—Palladium compounds without a metal-carbon linkage
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses the aminothiazole quinoline chiral ligand compounds and its preparation method and application that a kind of phenyl ring is skeleton.Using o-nitrobenzoic acid as raw material, chiral amino alcohol is chiral source, and the aminothiazole quinoline chiral ligand of the skeleton structure containing phenyl ring is easily synthesized very much through three steps " one kettle way ".Pd (II) complex compound made of the chiral ligand compound is in catalysis malonate and (E) -1, excellent enantioselectivity is shown in the asymmetric allyl group alkylated reaction of 3- diphenyl -2- allyl acetic acid ester, provides a kind of novel chiral ligands compound or catalyst for organic synthesis field.The structural formula general formula of aminothiazole quinoline ligand compound of the present invention is as follows:
Description
Technical field
The invention belongs to technical field of organic synthesis, it is related to a kind of aminothiazole quinoline chiral ligand compound and its preparation side
Method and application, and in particular to a kind of aminothiazole quinoline chiral ligand compound of the skeleton structure containing phenyl ring and preparation method thereof and
Application in asymmetric allyl group alkylated reaction.
Background technique
In the past few decades, asymmetric catalysis field achieves fast development, is the most significantly to develop a variety of tools
There is the chiral ligand of excellent catalysis characteristics.The exploitation of chiral ligand is the eternal theme of asymmetric catalysis field.Currently, chiral thiophene
Oxazoline ligand is a kind of chiral ligand being not yet fairly well-developed, and can be divided into single thiazoline, double according to the number of thiazoline ring
The three classes such as thiazoline and three thiazoline ligands.The document report synthesized and its applied in asymmetric syntheses in relation to thiazoline ligand
Road is less.Majority research is in conjunction with carrying out compared with the oxazole Phosphine ligands catalytic performance.It is worth noting that, 2014 shut out
Great Ming seminar [Peng, J.-H.;Du, D.-M.RSC Adv.2014,4,2061] discovery is studied in beta-ketoester and β-amide
Asymmetric fluorination reaction in, chiral Bisthiazoline ligand-Cu (OTf)2Complex compound is than corresponding oxazoline ligand-Cu (OTf)2
Complex compound provides higher enantioselectivity.Also illustrate that chiral thiazoline ligand is that a kind of chirality with very great development potentiality is matched
Body is not to be regarded as the analog of only oxazoline ligand.This seminar [Liu, L.et al.Tetrahedron
Asymmetry, 2012,22,550] the fragrant methene Bisthiazoline ligand of exploitation is in catalyzing indole and benzene methylene malonic acid ester
Excellent catalytic effect (99%yield, 99%ee) is shown in Friedel-Crafts alkylated reaction.Therefore it develops completely newly
There is ligand based on chiral thiazoline ring important theory and actual application to be worth.
Summary of the invention
The object of the present invention is to provide a kind of new aminothiazole quinoline chiral ligand compounds.With cheap ortho-nitrophenyl first
Acid is raw material, and chiral amino alcohol is chiral source, a kind of very succinct aminothiazole for synthesizing completely new skeleton structure containing phenyl ring
Quinoline chiral ligand compound.The general structure of aminothiazole quinoline ligand compound provided by the invention is as follows:
In Formulas I:
R1Selected from hydrogen, alkyl, aryl, halogen, nitro, cyano；
R2And R3It is respectively selected from hydrogen, alkyl, aryl, halogen ,-CO2R4Or-C (R5)2OR6, the R4Selected from alkyl or cycloalkanes
Base, aryl；R5Selected from hydrogen, alkyl or cycloalkyl, aryl；R6Selected from hydrogen, alkyl, aryl, trimethyl silicon substrate, fert-butyidimethylsilyl
Silicon substrate.
4 or 5 are asymmetric carbon atom on thiazoline ring.
Further, the aminothiazole quinoline chiral ligand compound is one of following I-a~I-e:
I-a:R1=H,R2=Ph,R3=H, chiral carbonoid: S
I-b:R1=H,R2=Bn,R3=H, chiral carbonoid: S
I-c:R1=H,R2=-CH(CH3)2,R3=H, chiral carbonoid: S
I-d:R1=H,R2=-CHCH2(CH3)2,R3=H, chiral carbonoid: S
I-e:R1=H,R2=-CH3,R3=H, chiral carbonoid: S
It is a further object to provide a kind of preparation methods of aminothiazole quinoline chiral ligand compound, with adjacent nitre
Yl benzoic acid is raw material, successively after three steps, " one kettle way " synthesis.Reaction equation and steps are as follows:
(1) acylated: by o-nitrobenzoic acid or ortho-aminobenzoic acid and acylating reagent thionyl chloride, oxalyl chloride, phosphoric
Phosphorus or phosphorus oxychloride 1:(1.2~20 in molar ratio) react 0.5 at 0~100 DEG C~for 24 hours to get arriving corresponding acid chloride intermediate；
(2) amidation: the acid chloride intermediate and corresponding chiral amino alcohol that step (1) is obtained in molar ratio 1:(1.2~
5) it is added in inert organic solvents tetrahydrofuran, methylene chloride or chloroform, in excessive organic base: pyridine, triethylamine, DBU；
Or inorganic base: NaOH, NaHCO3In the presence of, 0.5 is stirred to react in room temperature~-78 DEG C~for 24 hours, i.e. generation hydroxy amide II；
(3) cyclisation/reduction: 1:(2~20 in molar ratio the hydroxy amide II and phosphorus pentasulfide that step (2) is obtained) plus
Entering into atent solvent toluene or benzene, in the presence of organic base pyridine or triethylamine, 80~120 DEG C are stirred to react 2~48h,
Generate corresponding aminothiazole quinoline compound.
Further, o-nitrobenzoic acid (or ortho-aminobenzoic acid) is commercially available in above-mentioned steps (1).
Further, chiral amino alcohol is two kinds of configurations of L and D in above-mentioned steps (2), by natural or non-natural amino acid system
?.
Further, the dosage of inert organic solvents tetrahydrofuran, methylene chloride or chloroform is chiral ammonia in above-mentioned steps (2)
20~200 times of base alcohol mole.
Further, in the reaction of the step (3) while intramolecular dehydration cyclization, nitro is reduced into amino.
Further, in above-mentioned steps (3), the dosage of atent solvent benzene or toluene be hydroxy amide II mole 40~
100 times.The dosage of organic base pyridine or triethylamine is 4~30 times of hydroxy amide II mole.
A further object of the present invention is to provide Pd made of a kind of aminothiazole quinoline chiral ligand compound and metal salt
(II) or Pd (0) complex compound, for being catalyzed the application of following asymmetric allyl group alkylated reaction,
Advantages of the present invention:
Aminothiazole quinoline ligand compound preparation method simple process of the present invention, raw material is cheap and easy to get, avoids adjacent amino
Benzoic acid (belonging to country's control chemicals, be difficult to buy) is as starting material.Reaction condition is mild, easily operated.Gained
Aminothiazole quinoline ligand compound structure novel can form complex compound chiral catalyst with transition metal, show good
Asymmetry catalysis performance, in the asymmetric allyl alkane of catalysis malonate and (E) -1,3- diphenyl -2- allyl acetic acid ester
Excellent enantioselectivity is shown in glycosylation reaction, for organic synthesis field provide a kind of novel chiral ligands compound or
Catalyst provides strong experiment basis to develop new method of asymmetric synthesis, for development new medicine and novel pesticide and
New material provides strong synthetics.
Specific embodiment
The invention will be further described with reference to embodiments.Embodiment below is further explanation of the invention,
Rather than it limit the invention in any way.Those skilled in the art nonessential changes according to some of the above content of invention
It is all belonged to the scope of protection of the present invention into adjustment.
The synthesis of 1 ligand 2- of embodiment [(S) -4,5- dihydro -4- phenyl -2- thiazolinyl] aniline I-a
O-nitrobenzoic acid 0.5g (3.0mmol) is added in 50mL round-bottomed flask, thionyl chloride 0.5mL is heated to reflux
4h is cooled to room temperature, and vacuum rotary steam removes excessive thionyl chloride, obtains corresponding acid chloride intermediate, and with the dichloromethane of drying
Alkane 10mL dissolution.L- benzene glycinol 0.49g (3.6mmol) is added in another reaction flask, methylene chloride 30mL and triethylamine
5mL, system are cooled to 0 DEG C.The dichloromethane solution of acyl chlorides obtained by upper step is added thereto.It finishes, 4h is stirred at room temperature.Decompression rotation
Solvent is evaporated off, obtains corresponding hydroxy amide intermediate, is no longer further purified to be directly used in and react in next step.
30mL toluene and 5mL triethylamine is added, is heated to reflux state, phosphorus pentasulfide 2.66g is added altogether in three batches
(12mmol), charging finishes, and continues the 4h that flows back, end of reaction.It is cooled to room temperature, pours out reaction solution, ethyl acetate washing reaction
Bottle, and merge with liquid is poured out, vacuum rotary steam obtains crude product after sloughing solvent, directly passes through silica gel column chromatography separating-purifying (acetic acid
Ethyl ester/petroleum ether=1:3, v/v), obtain target product I-a: yellow solid, 62% yield；M.p.52~54 DEG C, 1H NMR(300MHz,CDCl3)δ7.60(dd,J=8.1,1.4Hz,1H),
7.54–7.31(m,5H),7.30–7.22(m,1H),6.80–6.68(m,2H),6.32(s,2H),5.82(t,J=9.0Hz,
1H),3.73(dd,J=10.9,8.5Hz,1H),3.21(dd,J=10.8,9.5Hz,1H).13C NMR(75MHz,CDCl3)δ
169.35,147.55,142.13,132.15,131.46,128.35,127.29,126.21,115.88,115.71,114.39,
80.57,39.01.
High resolution mass spectrum data: ESI-HRMS Calcd for C15H15N2S[M+H]+:255.0950,Found:
255.0954.
The synthesis of 2 ligand 2- of embodiment [(S) -4,5- dihydro -4- benzyl -2- thiazolinyl] aniline I-b
The L- benzene glycinol in example 1 is replaced with L- phenylalaninol, remaining obtains aminothiazole quinoline ligand with embodiment 1
I-b, yellow solid, yield 53%, m.p.70~72 DEG C, Its nucleus n-ness spectrum number
According to as follows:
1H NMR(300MHz,CDCl3)δ7.54(dd,J=8.1,1.3Hz,1H),7.45–7.17(m,6H),6.86–6.63
(m,2H),6.25(s,2H),5.09–4.91(m,1H),3.29(ddd,J=18.3,12.2,7.3Hz,2H),3.08(dd,J=
10.9,7.4Hz,1H),2.97(dd,J=13.5,7.9Hz,1H).13C NMR(75MHz,CDCl3)δ167.78,147.39,
138.68,132.03,131.25,128.97,128.18,126.12,115.86,115.64,114.50,78.79,40.80,
35.50.
High resolution mass spectrum data: ESI-HRMS Calcd for C16H17N2S[M+H]+:269.1107,Found:
269.1107.
The synthesis of 3 ligand 2- of embodiment [(S) -4,5- dihydro -4- isopropyl -2- thiazolinyl] aniline I-c
The L- benzene glycinol in example 1 is replaced with L- valerian ammonia alcohol, remaining obtains aminothiazole quinoline ligand i-with embodiment 1
C, yellow oil, yield 49%,Its nucleus n-ness spectrum data is as follows:
1H NMR(300MHz,CDCl3)δ7.45(dd,J=7.8,1.4Hz,1H),7.17(ddd,J=8.5,7.2,1.5Hz,
1H),6.75–6.60(m,2H),6.25(s,2H),4.44(ddd,J=9.7,8.4,6.8Hz,1H),3.29(dd,J=10.8,
8.4Hz,1H),2.99(dd,J=10.7,9.8Hz,1H),2.12–1.92(m,1H),1.12(d,J=6.7Hz,3H),1.04(d,
J=6.7Hz,3H).13C NMR(75MHz,CDCl3)δ166.96,147.29,131.91,131.02,115.83,115.57,
114.69,84.22,33.72,33.14,19.63,19.19.
High resolution mass spectrum data: ESI-HRMS Calcd for C12H17N2S[M+H]+:221.1107,Found:
221.1111.
The synthesis of 4 ligand 2- of embodiment [(S) -4,5- dihydro -4- isobutyl group -2- thiazolinyl] aniline I-d
The L- benzene glycinol in example 1 is replaced with L- leucinol, remaining obtains aminothiazole quinoline ligand i-with embodiment 1
D, yellow oil, yield 50%,Its nucleus n-ness spectrum data is as follows: 1H NMR
(300MHz,DMSO)δ7.59–7.49(m,1H),7.23(ddd,J=8.6,7.3,1.5Hz,1H),6.73(dtd,J=8.2,
3.5,1.1Hz,2H),6.31(br s,2H),4.89–4.70(m,1H),3.40(dd,J=10.7,8.0Hz,1H),2.94(dd,
J=10.7,8.4Hz,1H),2.02–1.79(m,2H),1.55(dt,J=13.5,6.9Hz,1H),1.10(d,J=6.5Hz,3H),
1.07(d,J=6.5Hz,3H).13C NMR(75MHz,CDCl3)δ167.17,147.61,132.29,131.37,116.15,
115.92,114.97,76.20,44.70,36.87,26.24,22.96,22.61.
High resolution mass spectrum data: ESI-HRMS Calcd for C13H19N2S[M+H]+:235.1263,Found:
234.1265
The synthesis of 5 ligand 2- of embodiment [(S) -4,5- dihydro -4- methyl -2- thiazolinyl] aniline I-e:
The L- benzene glycinol in example 1 is replaced with L- aminopropanol, remaining obtains aminothiazole quinoline ligand with embodiment 1
I-e, yellow oil, yield 55%,Its nucleus n-ness spectrum data is as follows:
1H NMR(300MHz,CDCl3)δ7.48(ddd,J=7.8,1.5,0.4Hz,1H),7.24–7.13(m,1H),
6.75–6.63(m,2H),6.24(br s,2H),4.90–4.74(m,1H),3.41(dd,J=10.7,8.0Hz,1H),2.92
(dd,J=10.7,7.7Hz,1H),1.47(d,J=6.7Hz,3H).13C NMR(75MHz,CDCl3)δ166.97,147.38,
131.99,131.15,115.86,115.66,114.55,72.85,37.82,20.62.
High resolution mass spectrum data: ESI-HRMS Calcd for C10H13N2S[M+H]+:193.0794,Found:
193.0796.
Embodiment 6: asymmetric allyl group alkylated
[Pd(η3-C3H5)Cl]2(0.0125mmol), anhydrous K OAc (0.1mmol) and chiral amino thiazoline ligand i-e
(0.03mmol) stirs 0.5h in methylene chloride (2.0mL) under nitrogen protection.At room temperature, (E) -1,3- hexichol is added
The dichloromethane solution (1.0mL) of base -2- allyl acetic acid ester, be subsequently added into methylmalonate (0.17mL, 1.5mmol) and
BSA(0.37mL,1.5mmol).After being stirred at room temperature for 24 hours, with 10mL saturated ammonium chloride solution quenching reaction, organic phase, water are separated
It is mutually extracted with ethyl acetate (2 × 10mL), merges organic phase, anhydrous sodium sulfate is dry.Decompression boils off solvent, and residue is through silica gel
Column chromatography for separation (petrol ether/ethyl acetate=5/1, v/v), obtains colorless oil.88% yield, 92%ee value (Daicel
Chiralcel AD-H,n-hexane/i-PrOH=90:10,1.0mL/min,254nm):tR(minor)=14.43min,tR
(major)=19.77min).1H NMR(300MHz,CDCl3):δ7.35-7.17(m,10H,Ar-H),6.47(d,J=
15.75Hz,1H,-CH=),6.32(dd,J=8.43Hz,15.90Hz,1H,-CH=),4.26(dd,J=8.43Hz,10.80Hz,
1H,CH),3.95(d,J=10.80Hz,1H,CH),3.71(s,3H,-OCH3),3.52(s,3H,-OCH3)。
Claims (6)
1. a kind of aminothiazole quinoline chiral ligand compound, which is characterized in that it is the hand of skeleton that the ligand compound, which has phenyl ring,
Property neighbour's aminothiazole quinoline structure, general structure are as follows:
In Formulas I:
R1And R3For hydrogen；
R24 are S configuration asymmetric carbon atom on methyl, isopropyl, isobutyl group, phenyl and benzyl, thiazoline ring.
2. the preparation method of aminothiazole quinoline chiral ligand compound according to claim 1, which is characterized in that the side
Method is using o-nitrobenzoic acid as raw material, successively after three acylation, amidation and cyclisation/reduction steps, " one kettle way " synthesis；
Three steps are successively acylation, amidation, cyclisation/reduction, " one kettle way " synthesis, reaction equation and steps are as follows:
(1) acylated: by o-nitrobenzoic acid and acylating reagent thionyl chloride, oxalyl chloride, phosphorus pentachloride or phosphorus oxychloride by mole
Than 1:(1.2~20) 0~100 DEG C react 0.5~for 24 hours to get arrive corresponding acid chloride intermediate；
(2) step (1) amidation: is obtained into acid chloride intermediate and corresponding chiral amino alcohol 1:(1.2~5 in molar ratio) it is added
Into inert organic solvents tetrahydrofuran, methylene chloride or chloroform, in excessive organic base: pyridine, triethylamine or DBU；Or nothing
Machine alkali: NaOH or NaHCO3In the presence of, 0.5 is stirred to react in room temperature~-78 DEG C~for 24 hours, i.e. generation hydroxy amide II, wherein R
For R2；
(3) cyclisation/reduction: by 1:(2~10 in molar ratio hydroxy amide II and phosphorus pentasulfide that step (2) obtains) it is added to
In atent solvent toluene or benzene, in the presence of organic base pyridine or triethylamine, 80~120 DEG C are stirred to react 2~48h, i.e., raw
At corresponding amino-thiazol quinoline ligand compound；Wherein in Formulas I:
R1And R3For hydrogen；
R24 are S configuration asymmetric carbon atom on methyl, isopropyl, isobutyl group, phenyl and benzyl, thiazoline ring.
3. the preparation method of aminothiazole quinoline chiral ligand compound according to claim 2, which is characterized in that the step
Suddenly o-nitrobenzoic acid is commercially available in (1).
4. the preparation method of aminothiazole quinoline chiral ligand compound according to claim 2, which is characterized in that the step
Suddenly the dosage of inert organic solvents tetrahydrofuran, methylene chloride or chloroform is the 20~200 of chiral amino alcohol mole in (2)
Times.
5. the preparation method of aminothiazole quinoline chiral ligand compound according to claim 2, which is characterized in that the step
Suddenly in the reaction of (3), while intramolecular dehydration cyclization, nitro is reduced into amino.
6. the preparation method of aminothiazole quinoline chiral ligand compound according to claim 2, which is characterized in that the step
Suddenly in the reaction of (3), the dosage of atent solvent benzene or toluene is 40~100 times of hydroxy amide II mole, organic base pyridine
Or the dosage of triethylamine is 4~30 times of hydroxy amide II mole.
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